Throughout this application, various publications are referenced to and the disclosures of these publications are hereby incorporated by reference into this application in order to more fully describe the state of the art as known to the skilled therein as of this date of the invention described and claimed herein.
This invention relates to a composition comprising extracts of flos lonicerae, fructus forsythiae and radix scutellariae, uses and preparation thereof. This composition could be used for the inhibition of influenza virus, parainfluenza virus, herpes I virus and herpes II virus.
Influenza is the most frequent cause of acute respiratory illness that could require medical intervention. It affects all age groups and it can recur to any individual. A study involving some residents of a nursing home that suffer from respiratory viral diseases was conducted between 1988 and 1999. The results showed a thirty-day mortality of 4.7% (15/322) for influenza A, 5.4% (7/129) for influenza B, 6.1% (3/49) for parainfluenza type I, 0% (0/26) for parainfluenza type II, type III and type IV, 0% (0/26) for respiratory syncytial virus (RSV), and 1.6% (1/61) for rhinovirus. The herpes simplex virus infection is an important risk factor caused cervical carcinoma, AIDS, Alzheimer""s disease. The rates of herpes simplex virus (HSV) infection are rising, the highest prevalence being in the group infected with the Human Immunodeficiency Virus (HIV).
During the past three decades, efforts to prevent and control influenza have focused primarily on the use of inactivated influenza vaccines in elderly people and in individuals with chronic medical conditions. However, the continuing impact of influenza in these and other population groups has motivated the development of novel approaches for prevention and control of influenza. Several important advances in the field of influenza have occurred in the last few years. New antiviral drugs based on the structure of the neuraminidase molecule were assessed in clinical trials and found to be effective against influenza A and B viruses. In recent year, the research and development of nature products for influenza virus and herpes simplex virus are gradually increasing in importance. Studies from Dr. Mori K, Kampo Pharmacology Department, Central Research Laboratories, Tsumara of Japan showed that the Hochu-ekki-to (TJ-41), a Japanese herbal medicine was found to increase the survival rate of mice, prolong the mean survival days, and suppress viral growth in bronchoalveolar labage fluid (BALF). This medicine inhibited the lung index (lung consolidation) four days after the mice were infected with influenza. The agent had been administered 7 days before injection of the virus and 4 days after injection. The results suggested that the TJ-41 exerts its inhibitory effects over the influenza virus infection via enhancement of the host immune responses in this experimental murine system. Dr. Mantani N, Department of Japanese Oriental Medicine, Toyama Medical and Pharmaceutical University, conducted a vital fluorescence microscopic study. It showed that the extract of Ephedrae herba (EHext) inhibited acidification of endosomes and lysosomes in a concentration-dependent manner (100-400 mg/ml). Moreover the growth of influenza A/PR/8/34 (HlN1) (PR8) virus was inhibited when the cells were treated with EHext for one hour immediately after infection, or treated as early as 5-10 min after the infection.
Gingyo-san is a natural product containing extracts from seven medicinal plants and fermented soybeans in a specific ratio. It has been used as a therapeutic agent for the common cold in China. Dr. Kurokawa M, Department of Virology, Toyama Medical and Pharmaceutical University of Japan, found that two components extracted from Glycyrrhizae radix and Arctii Fructus presented anti-influenza viral activities in mice infected with influenza A2 virus. Dr. Yamada H, Oriental Medicine Research Center, Kitasato Institute of Japan studied the anti-virus activity of Sho-seiryu-to (SST). He suggested that SST was useful for influenza virus infection on aged people and for cross-protection of subtypes of influenza A viruses and influenza B virus, and was also useful for the treatment of patients who had a history of influenza virus infection and/or influenza vaccination. Dr. Hayashi K, Department of Virology, Toyama Medical and Pharmaceutical University studied the activities of thirteen sesquiterpenes isolated from Tripterygium wilfordii Hook fil. var. regelii Makino against herpes simplex virus type 1 (HSV-1) in vitro. He found that the triptofordin C-2 suppressed viral protein synthesis of infected cells when added at the early steps of the HSV-1 replication and exerted inhibition of translation of the transcripts of the immediate early genes. Radix bupleuri, a Chinese medicinal herb used for the treatment of influenza, malaria and menstrual disorders, was extracted with hot water and separated into five different fractions (RB, RBI, RBII, RBIII and RBIV) by stepwise alcohol precipitation. Dr. Kok LD, Department of Biochemistry, Chinese University of Hong Kong, found that RBIII exhibited a potent activating effect on the cytotoxic activity of macrophages, NK and LAK cells against tumor cells in his studies. Dr. Ball MA investigated the antiviral effect of the Keishi-ni-eppi-ichi-to (TJS-064) in mice infected with the influenza A2 (H2N2) virus. The result showed that pulmonary consolidations, virus titers in lung tissues and HAI titers in sera of infected mice treated with TJS-064 were all significantly lower compare with those of infected mice treated with saline. Dr. Fu HY presented the decoction of Gui Zhi Tang (DGZT), which had the action of bidirectional regulation and normalization in polyhidrosis induced by aminopyrine or in the case of hypohidrosis induced by ropineonrats.
The product obtained from this invention is an effective agent for inhibition of influenza virus, parainfluenza virus, herpes I virus and herpes II virus. The composition of this Chinese herbal medicine comprises three herbal components: Radix Scutellariae, Fructus Forsythiae and Flos Lonicerae. The pharmacological characteristics and efficacy relating to the compositions had been confirmed in previous studies.
Wang Y H, the Second Hospital of Harbin Medical University, presented a result of clinical research in his publication. Two hundred and two cases of acute respiratory tract infection (ARI) were treated with Shuanghuanglian (SHL) aerosol, an antiviral agent. Among them, 64% of the cases were caused from Respiratory Syncytial Virus (RSV). The virostatic and bacteriostatic tests were done in vitro by the cell culture method. The results showed that SHL could inhibit the RSV, parainfluenza I-IV and 23 kinds of pathogenic bacteria such as the Staphylococcus aureus. The bacteriostatic effect was positively correlated to the SHL concentration. Experimental studies showed that SHL could enhance the NK cell activity, promote the production of alpha-interferon and raise the rate of lymphocyte transformation. The controlled observation on SHL preparation with various dosage-forms revealed that the SHL aerosol was effective in treating early ARI. This drug showed better results when compare to the results from the injections and oral liquor symptom etiologically (P less than 0.01). Its effective rate was 96%.
Some studies were conducted with herbal products for anti-inflammation or/and anti-virus, which include herbal components comprising Radix Scutellariae or Fructus Forsythiae or Flos Lonicerae. However, there were differences of the formula, content and efficiency of effective composition compared with the invention.
U.S. Pat. No. 5,908,628 refers to a therapeutic composition for the treatment of pain, fever and inflammation, which includes some herbal components, one of them is Fructus Forsythiae. The percentage of Fructus Forsythiae is only 5-15% and the range of weight is 170-190 g in the composition.
In U.S. Pat. No. 5,834,000, a pharmacologically effective composition was studied. The composition, comprising Isatides tinctoria, Forsythia fructus, Lonicera flos et al, showed antiviral and antimicrobial activities. The weight percent of Isatides tinctoria is about 37.5%, and 5% of Forsythia fructus and Lonicera flos. Forsythia fructus and Lonicera flos can relieve sore throat symptoms and reduce fever without unwanted side effects. There is a difference in the percentage and composition of effective ingredients when compared with this invention of which the percentage of Forsythia fructus is about 50% and for the Lonicera flos is 25%.
U.S. Pat. No. 5,989,556 pertains to the compositions derived from Chinese herbal medicines, medicinal plants and extracts thereof, which are used for treatment of infected animals, especially those with hepatitis B and C viruses (HBV and HCV), and Human Immunodeficiency Virus (HIV). The compositions contain forsythiae fructus, lonicerae flos or scutellariae in various groups.
The SHL agent is extracted with ancient techniques that have been used in traditional Chinese medicine for a long period of time. In the early 70xe2x80x2s, the SHL was used to treat upper respiratory tract infection. The statistics from Pediatrics Department of Haerbin Medical University of China indicated that the effective rate of pediatric pneumonia was about 92.5% and the cure rate was around 80.8%. In the early 90xe2x80x2s, the Ministry of Public Health of China approved different kinds of devices for the use of SHL such as powder injection, water injection, oral liquid, aerosol and tablet. But none of these devices were very effective in the way they were produced and administered.
This invention is the second development of the SHL tablet. The technique of preparation, composition and efficacy for the treatment of inhibition of influenza virus, parainfluenza virus, herpes I virus and herpes II virus were further improved in this invention.
This invention refers to an herbal composition that inhibits the influenza virus, parainfluenza virus, herpes I virus and herpes II virus. This invention derives from an herbal composition. Wherein said composition comprises Flos Lonicerae, Fructus Forsythiae, Radix Scutellariae. This invention includes a method for identification with HPLC and the characteristic peaks of the compositions of the raw materials, drug substances and drug product. The invention refers to a special extraction, wherein said extraction comprises CO2 supercritical fluid extraction consisting of Flos Lonicerae and Fructus Forsythiae, subboiling aqueous extraction, flocculation and alcohol precipitation. The invention refers to a unique intermediate formulae, wherein said formulae comprises about 90-180 g of drug substance of 10-60 g of Flos Lonicerae and Fructus Forsythiae, 10-60 g of supercritical extracta of Flos Lonicerae and Fructus Forsythiae and about 30-50 g of Radix Scutellariae extract. This current preparation was made more effective than the one used in previous techniques.